23andMe is a personal genomics company with a mission of accelerating medical discoveries by empowering consumers to participate in research. At the heart of this mission is the 23andMe research engine, a novel platform for conducting genetic studies that allows individuals to participate in genetic research by enrolling in the company's Personal Genome Service(R) and taking online surveys. Over 80,000 genotyped individuals have contributed data, and this number is growing by over 50,000 each year. Our initial publications have shown the power and efficiency of this web- based approach for discovering novel genetic associations for a range of traits and diseases. These early successes, however, only made partial use of the rich and rapidly expanding 23andMe database. Our current challenge is to fully exploit the genetic and disease information that we can collect to accelerate the pace of human genetic research. To achieve this goal, we propose, in Phase I, to measure and improve the reliability of our self- reported data, to analyze and organize survey responses for hundreds of new traits, and to extract information of greater depth and quality from the previously collected genetic data. Successful completion of Phase I will demonstrate the feasibility of our web-based approach for studying a broad range of conditions. Building on this foundation, in Phase II we will develop a set of new surveys and implement novel web-based data collection tools to efficiently gather longitudinal data. Capitalizing on the upcoming explosion of whole-genome sequence data, we will also greatly improve the depth of our genetic data through statistical imputation and imputation via identity-by-descent. At the end of the proposed research, we expect the 23andMe database to grow to over 200,000 genotyped individuals with detailed health and trait information. Applying computational sequencing methods to these data will deliver the informational equivalent of thousands of whole- genome sequences at very low cost. This database has the potential to yield hundreds, if not thousands, of novel genetic associations for diseases and traits, leading to a greater biological understanding of these conditions, potential drug targets, and improved tools to predict an individual's genetic risk of disease. Using the diverse 23andMe cohort, we will extend genetic research to understudied populations. A key commercial outcome of the project will be a database and research engine that is more valuable to potential research partners. Furthermore, discoveries will drive new reports for 23andMe customers, thus increasing the value of the Personal Genome Service(R). PUBLIC HEALTH RELEVANCE: Genetic research has already produced biological discoveries and personalized treatments, but the field has far to go. This proposal aims to accelerate that research by taking advantage of 23andMe's growing membership of research participants who provide a wide range of personal as well as genetic information. The study will enable 23andMe to greatly increase the scope of their research and lead to new understanding of how genetics impacts human disease.